Cetuximab Sarotalocan Sodium (Genetical Recombination)

Rakuten’s lead therapy, ASP-1929, is an antibody-dye conjugate comprising of an epidermal growth factor receptor (EGFR) antagonist antibody, cetuximab, and a light activatable dye, IRDue 700DX. Image Credit: Poetra.RH / Shutterstock. US-based Rakuten Medical has announced positive interim data from the Phase Ib/II trial of its photoimmunotherapy, ASP-1929, in combination with Merck & Co (MSD)’s Keytruda (pembrolizumab) in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). Following the positive results, the company now plans to start a global Phase III clinical trial evaluating the combination therapy of ASP-1929 and Keytruda as first-line therapy in recurrent HNSCC in the second half of this year. The study’s primary endpoint will be overall survival. The results from the open-label Phase Ib/II study (NCT04305795) will be presented at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago from 31 May to 4 June. ASP-1929 is an antibody-dye conjugate comprising of an epidermal growth factor receptor (EGFR) antagonist antibody, cetuximab, and a light-activated dye, IRDue 700DX. The therapy is activated locally by inducing a photochemical reaction when illuminated with red light using a laser device system. This potentially causes membrane damage in cancer cells, leading to selective necrosis of cancer cells. Cetuximab is independently sold under the brand name Erbitux by Bristol Myers Squibb as a treatment for late-stage HNSCC and metastatic colorectal cancer . See Also: South Korea’s MFDS approves Eisai-Biogen’s LEQEMBI for Alzheimer’s ASCO 2024: MediLink’s NSCLC and breast cancer ADC shows early safety success ASP-1929 received fast track designation from the US Food and Drug Administration (FDA) in 2018. It was approved as a treatment for unresectable locally advanced or recurrent head and neck cancer in Japan. As of the data cut-off of 31 August 2023, 18 out of 19 patients received both therapies in the Phase Ib/II trial. Median overall survival and duration of response were not reached as of the data cut-off. The therapy had an objective response rate (ORR) of 35.3%, with four complete and two partial responses. At 24 months, the treatment had an estimated survival rate of 52.4%. Commonly observed serious adverse reactions included dysphagia and tongue oedema. While there were no fatal events, two Grade 4 events, namely laryngeal oedema and tumour haemorrhage, were observed due to advanced disease. In March, Rakuten raised $119m in a Series E financing round to develop its Alluminox drug discovery platform and fund the Phase III ASP-1929 monotherapy trial (NCT03769506). The open-label Phase III study is expected to enrol approximately 275 participants with recurrent HNSCC who have received at least two prior lines of therapy.

Overall survival rate estimated at 24 months was 52.4% with generally tolerated safety profile Completed a Type B End-of-Phase 2 (EOP2) meeting with the US FDA for the combination (ASP-1929 photoimmunotherapy and anti-PD-1) in the first-line recurrent HNSCC setting and reviewed the key details of a multi-regional registrational study Rakuten Medical plans to initiate the global Phase 3 clinical trial with a primary endpoint of OS in 2H 2024 SAN DIEGO, May 24, 2024 /PRNewswire/ -- Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeting photoimmunotherapy based on its proprietary Alluminox™ platform, today announced the updated safety and efficacy findings from an interim evaluation of an open-label Phase 1b/2 study (ASP-1929-181/ClinicalTrials.gov Identifier: NCT04305795) of photoimmunotherapy using ASP-1929 in combination with anti-PD-1 for recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). The data will be presented in a poster at the 2024 American Society of Clinical Oncology Annual Meeting (ASCO 2024) on June 2, 2024. The updated interim evaluation (data cut-off: August 31, 2023) of 19 enrolled patients in ASP-1929-181 study suggests that the novel treatment approach of ASP-1929 photoimmunotherapy in combination with anti-PD-1 showed promising early results in patients with locoregional and/or metastatic HNSCC. Median overall survival (OS) was not reached at data cut-off, with an estimated survival rate of 52.4% at 24 months, and an objective response rate (ORR) of 35.3%. Adverse events were generally manageable, and the combination therapy was generally tolerated with an absence of synergistic serious adverse events. The encouraging early efficacy and safety outcomes warrant additional clinical studies to substantiate and reinforce these interim findings. Rakuten Medical recently completed a Type B End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) for the combination of ASP-1929 photoimmunotherapy and anti-PD-1 in the first-line recurrent HNSCC setting and discussed the key details for a multi-regional registrational study. Based on these results, Rakuten Medical plans to initiate this global phase 3 clinical trial with a primary endpoint of OS in the second half of 2024. Disclaimer: These interim findings may change upon completion of follow-up and final data analysis. Key findings [Efficacy] Clinically meaningful activity was observed Median Overall Survival (OS) was not reached, with an estimated survival rate of 52.4% (95% CI: 25.9-73.4) at 24 months The objective response rate (ORR) was 35.3% (6 patients, 95% CI: 14.2-61.7), which included 4 complete responses (CR) (23.5%, 95% CI: 6.8-49.9) and 2 partial responses (PR) (11.8%, 95% CI: 1.5-36.4) Median time to response of 1.4 months Median progression-free survival (PFS) was at 2.9 months (95% CI 1.4-14.6) [Safety] Adverse events were manageable and generally tolerated No fatal serious adverse events (SAEs) Two Grade 4 SAEs: laryngeal edema related to photoimmunotherapy and tumor hemorrhage unrelated to study treatment, both of which resolved No synergistic SAEs due to ASP-1929 and anti-PD-1 Upcoming Rakuten Medical's Poster Presentation at ASCO Abstract Title: Recent safety and efficacy findings from a phase 1b/2 open-label combination study of ASP-1929 photoimmunotherapy with anti-PD-1 therapy in EGFR-expressing advanced head and neck squamous cell carcinoma (HNSCC) Abstract Number: 6083 Abstract Link: Session Name: Poster Session – Head and Neck Cancer Session Date: Sunday, June 2, 2024 Session Time: 9:00 a.m. – 12:00 p.m., CDT First Author: David M. Cognetti, Department of Otolaryngology – Head and Neck Surgery, Thomas Jefferson University, US Location: Exhibit Hall A, Poster Board #399 About Rakuten Medical, Inc. Rakuten Medical, Inc. is a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, which, in pre-clinical studies, has been shown to induce rapid and selective cell killing and tumor necrosis. Alluminox therapies have not yet been approved outside of Japan. Rakuten Medical is committed to its mission to conquer cancer by delivering its innovative treatments as quickly as possible to as many patients as possible all over the world. The company has offices in 5 countries/regions, including the United States, where it is headquartered, Japan, Taiwan, Switzerland and India. For more information, visit . About Alluminox™ platform The Alluminox™ platform is an investigational technology platform based on a cancer therapy called photoimmunotherapy, which was developed by Dr. Hisataka Kobayashi and team from the National Cancer Institute in the United States. Rakuten Medical is developing the Alluminox platform as a technology consisting of a drug, device, and other related components. The drug component of the platform consists of a targeting moiety conjugated with one or more dyes leading to selective cell surface binding. The device component consists of a light source that locally illuminates the targeted cells with light to transiently activate the drug. Pre-clinical data have shown that this activation elicits rapid and selective necrosis of targeted cells through a biophysical process that compromises the membrane integrity of the targeted cells. Therapies developed on the Alluminox platform may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted cancer cells and/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Outside of Japan, Alluminox therapies have not yet been approved by any regulatory authority. About ASP-1929 Rakuten Medical's first pipeline drug developed on its Alluminox™ platform is ASP-1929, an antibody-dye conjugate comprised of the antibody cetuximab and IRDye® 700DX, a light activatable dye. ASP-1929 binds to epidermal growth factor receptor (EGFR), a cancer antigen expressed in multiple types of solid tumors, including head and neck, breast, lung, colorectal, prostate and pancreatic cancers. After binding to cancer cells, ASP-1929 is locally activated by illumination with red light (690 nm), emitted by a laser device system to produce a photochemical reaction. This reaction is believed to cause damage to the membrane of cancer cells, leading to selective necrosis of cancer cells. ASP-1929 has received Fast Track designation from the U.S. Food and Drug Administration (FDA) in January 2018, and is currently under investigation in a global Phase 3 clinical trial for recurrent head and neck cancer. In Japan, ASP-1929 received marketing approval from the Japanese Ministry of Health, Labor, and Welfare for unresectable locally advanced or recurrent head and neck cancer in September 2020, under the Sakigake Designation System and the Conditional Early Approval System. Outside of Japan, ASP-1929 has not yet been approved by any regulatory authority. Forward Looking Statements This press release contains forward looking statements that correspond to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements include various risks, uncertainties, and assumptions that may cause Rakuten Medical's business plans and results to differ from the anticipated results and expectations expressed in these statements. These "forward looking statements" contain information about the status and development of our products, including the Alluminox™ platform, as well as other regulatory and marketing authorization efforts, the potential benefits, efficacy, and safety of therapies created using the Alluminox platform, and the status of regulatory filings. The approval and commercial success of the product may not be achieved. Forward looking statements relate to the potential benefits, efficacy, and safety of our therapies, and the status of regulatory filings. Such statements may include words such as "expect," "believe," "hope," "estimate," "looks as though," "anticipate," "intend," "may," "suggest," "plan," "strategy," "will," and "do", and are based on our current beliefs. In addition, this press release uses terms such as "important," "notable," and "abnormal" to express opinions about clinical trial data. Ongoing clinical trial studies include various risks and uncertainties, in particular, problems that arise during the manufacturing stage of our therapies, the occurrence of adverse safety events, situations in failure to demonstrate therapeutic benefits, and other various risks and uncertainties, both reasonable and unreasonable. For this reason, actual results, including regulatory approvals and uncertainties in the commercialization process of our therapies, may differ from published information. Except to the extent required by applicable law, we undertake no obligation to publicly update this or any other forward-looking statement, whether because of new information, future developments or events, changes in assumptions, changes in the factors affecting forward-looking statements. If one or more forward-looking statement(s) is updated, no inference should be drawn that additional updates will be made to those or other forward-looking statements. Contact Us SOURCE Rakuten Medical, Inc.